378 genetic markers were examined and a linkage was found "between bipolar illness vulnerability and loci on chromosomes 15q14 and 7q11.
Lithium: The literature was reviewed of patients taking lithium long term to patients that discontinued it. "Suicidal acts rose 22-fold, and fatalities increased 14-fold, within the first year after discontinuing the lithium." There are increased cases of goiter in 100 patients taking lithium that was related to dose and duration. This was prevented by thyroxine.
Bipolar Disord 1999 Sep;1(1):5-10
Perspectives on lithium treatment of bipolar disorder: action, efficacy, effect on suicidal behavior.
The Psychiatric Hospital, Risskov, Denmark
In bipolar disorder the choice of prophylactic drug must be based on a weighing of efficacy against tolerability, interactions, ease of management, use during pregnancy and lactation, and expense. Lithium should be the preferred prophylactic drug in patients with typical bipolar disorder and in patients who are at high risk of committing suicide, that is, patients with severe depressions or depressions combined with persistent suicidal ideas or with suicide attempts in the past.
Mood stabilizers taken with newer (second generation) antidepressants induce mania less than older antidepressants - tricyclics and MAOI.
Bupropion (Wellbutrin), sertraline (Zoloft), and venlafaxine (Effexor) are examined in consumers with the bipolar disorder who experience "break through depression," even though medicated.
There is a moderate antidepressant response in 33% and a 12% rate of triggering mania in this study of 100 bipolars.
Buproprion (Wellbutrin) vs. Desipramine (Norpramin) were studied. The rate of cycling between mania and hypomania was significantly greater in the Desipramine group (37%). Buproprion (13%,p<0.05).
Paxil studied in a randomized, controlled six week trial. It was found to be "equally effective for depression breaking through ongoing mood stabilizer treatment as an addition of a second mood stabilizer, typically valproate to lithium, or vice versa."
"...the risk of depressive relapse for 27 bipolar patients after antidepressant discontinuation was 67% versus 39% in the 18 patients who" stayed on their antidepressants.
The treatment of combining one or more mood stabilizers with an antidepressant to prevent manic episodes, needs to be explored further.
"...using the newer antidepressants earlier to supplement mood stabilizers should be considered."
New medication and combining medications can produce remarkable improvement.
Lamotrigine (Lamictal) has assisted many consumers whose illness has not responded to other treatments. (Frye et al, 2000, J Clin Psychopharmacol, in press; Calabrese et al., 1999, J Clin Psychiatry 60: 79-88).
Proceed slowly with Lamictal to reduce risk of rash and other side effects.
Lamotrigine (Lamictal) was superior to both gabapentin and placebo in a six-week monotherapy trial for refractory patients.
437 outpatient study, double-blind, placebo-controlled; Lamotrigine is equal to desipramine and superior to placebo in unipolar depression.
Gabapentin (Neurontin) is helpful for residual manic and depressive symptoms, but not rapid cycling. Neurontin has better response with patients who are associated with younger age, shorter duration of illness, and lower initial body weight. Gabapentin failed to exceed placebo in an outpatient study of acute mania.
Gabapentin is not an effective medication for acute mania. Study: 10 wk., double-blind, placebo-controlled trial dosed between 900 and 3600 mg/day. Gabapentin was "not superior to the placebo for bipolar I symptoms of hypomania, mania, or mixed states."
Gabapentin has also been "effective in some anxiety disorders including social phobia and is widely used for adjunctive treatment in pain syndromes."
218 patient study of Gabapentin in the treatment of bipolar disorder shows that if it is "combined with antidepressants, neuroleptics, lithium, and other anticonvulsants, had a high rate of response in combination (69%) and in monotherapy (42%)."
Bipolar Disord 1999 Sep;1(1):61-5
Altshuler LL, Keck PE Jr, McElroy SL, Suppes T, Brown ES, Denicoff K, Frye M, Gitlin M, Hwang S, Goodman R, Leverich G, Nolen W, Kupka R, Post R.
UCLA Mood Disorders Research Program, UCLA Medical Plaza, CA 90095-7057, USA
Gabapentin appears to have acute anti-manic and anti-depressant properties as an adjunctive agent for refractory bipolar illness. Prospective double-blind studies are needed to further delineate its acute efficacy when used as monotherapy and its prophylactic efficacy as monotherapy or in conjuction with other mood stabilizers.
Divalproex (Depakote) vs. Lithium were both equally effective in 43 patients. The patients that did not respond to Lithium, responded to Depakote and vice versa. "Depakote monotherapy was notably effective in treating depressive symptoms."
Topiramate (Topamax) find a 56% much or very much improved response in "16 patients after 6 weeks, four of the 16 had unpleasant sense of touch and two had word finding difficulties," in the treatment of bipolar disorder. All patients lost weight at an average of 10 pounds.
"Dr. R. McIntyre and colleagues at the Centre for Addiction and Mental Health, Toronto, compared topiramate (50-300 mg/day) to bupropion SR (Wellbutrin, 100-400 mg/day) for eight weeks as adjuncts to mood stabilizers in 26 bipolar out patients with major depression. Both bupropion SR and topiramate showed a significant reduction in depressive symptoms and were not statistically different from each other. No patients switched into a manic episode on either treatment. These preliminary results suggest that topiramate may have comparable antidepressant activity to bupropion SR, a remarkable finding if replicated."
Mexiletine (Mexitil) has anticonvulsant, antiarrhythmic, and analgesic properties. In a study of 13 treatment resistant bipolars at doses from 200 - 1200 mg/day had a full response in 45% of patients. Another study: 8 out of 26 patients treated with Mexiletine had a positive therapeutic effect.
ECT (Electro Convulsive Therapy)
"...low dose, right unilateral (one-sided) was ineffective in two different studies of major depression (i.e., 23% improvement or 17% improvement respectively). However, high dose right unilateral ECT was as effective as bilateral (two-sided) ECT, and bilateral ECT clearly produced more lasting amnesia and memory defects. (Sackeim et al, 2000; Arch Gen Psychiatry 57: 425-434).
rTMS and ECT are generally equally effective in "patients with nondelusional major depression.
ECT superior to patients with delusional depression than rTMS.
Study of 10 bipolar brains during autopsy compared with "11 nonpsychiatric control subjects.
Dr. Rajkowska found decreased density of layer 3 in the dorsolateral pre-frontal cortex (Brodman's area nine), comprised of a decrease in the numbers of pyramidal cells but not other neuronal elements, a decrease in glial cell density, and an increase in glial size."
"...bipolar patients showed: 1) decreased dorsolateral prefrontal cortex NAA bilaterally; 2) decreased prefrontal white matter NAA bilaterally; and, 3) increased thalamic NAA bilaterally.
These data thus supplement a growing amount of structural imaging data suggesting alterations in size or chemistry of the prefrontal cortex, amygdala, and hippocampus in bipolar patients compared with controls."
Olanzapine (Zyprexa) was statistically significantly superior to placebo in the treatment of rapid cycling Bipolar I patients.
Bipolar Disord 2000 Sep;2(3 Pt 1):196-9
Ghaemi SN, Cherry EL, Katzow JA, Goodwin FK.
Harvard Bipolar Research Program, Massachusetts General Hospital, Consolidated Department of Psychiatry, Boston 02114, USA.
"Olanzapine appears to be moderately effective in open add-on treatment in patients with mainly depressive symptoms. Accumulating evidence suggests that olanzapine, and atypical antipsychotics in general, possess mild to moderate adjunctive antidepressant properties."
"Dr. R. Baker and co-workers from Lilly Research Laboratories and Harvard Medical School found that in two inpatient double-blind, randomized trials investigating the efficacy of olanzapine for acute mania, worsening of mania occurred more often on placebo than on olanzapine, in contrast to previous reports in open trials that olanzapine induced or exacerbated mania."
"Dr. J. Frazier from Harvard Medical School and colleagues conducted a study of olanzapine monotherapy (2.5-20 mg/day) in 23 juvenile bipolar patients (ages 5-14) with mania or mixed symptoms. Sixty-one percent of patients responded, and 22 (96%) of 23 completed the study. Clinically significant increases in weight occurred in some patients, however."
"Dr. M. Tohen of Lilly Research Laboratories and Harvard Medical School, along with colleagues from a variety of universities, performed several studies with olanzapine. A three-week, double-blind study of olanzapine (5-20 mg/day) versus valproate (500-2500 mg/day) in hospitalized manic patients showed a statistically significant greater improvement on olanzapine."
6 month follow up showed fewer bipolar episodes, higher social functioning, and better coping strategies "compared with the control group that received treatment as usual. There was no evidence that the improvement in the therapy group was due to more medications being prescribed."
Being able to identity early stages of relapse is very effective in regards to the length of time the relapse lasts.
"To date there are six controlled studies of CBT interventions with children. All are school-based studies of children with self-reported (but not with diagnosed) depression. Five of the six support the efficacy of CBT in reducing depressive symptoms. There is considerable variation in the nature of the CBT interventions.
"There are nine controlled or comparative studies of CBT for adolescent depression, seven of which found CBT efficacious at the end of acute treatment. Most include adolescents with diagnosed depressive disorders, and only one was conducted in a school setting.
"...there is a question about whether CBT, medication, or combination treatment is more efficacious with depressed teenagers or with certain subgroups of these young people."
John F. Curry, Duke University Medical Center "Specific Psychotherapies for Childhood and Adolescent Depression"
17 to 24 year olds with bipolar spectrum disorders "reported higher lifetime rates of anxiety, substance abuse, Attention Deficit-Hyperactivity Disorder (ADHD), and eating disorders in bipolar than in unipolar depressed participants. Women with bipolar disorder had higher rates of anxiety (85% vs. 41%), ADHD (18% vs. 5%), and eating disorders (15% vs. 0%) than men with bipolar disorder, but not substance abuse disorders (41% vs. 32%)."
"A recent National DMDA [Depressive and Manic-Depressive Association] survey of people with bipolar disorder indicated that the average length of time from onset of symptoms to correct diagnosis was 10 years."
Lydia Lewis, National DMDA "Unmet Needs in Diagnosis and Treatment of Mood Disorder in Children and Adolescents"
"More than 400 case reports and small trials have been reported on the treatment of bipolar children and adolescents...Positive reports have been published for lithium, divalproex, and carbamazepine; however, many reports have been based on retrospective chart reviews and small open-label studies...few placebo-controlled trials for bipolar, manic or mixed, in children and adolescents have been conducted."
Graham J. Emslie and Tarym L Mayes, University of Texas Southwestern Medical Center "Mood Disorder in Children and Adolescents: Psychopharmacological Treatment"
Added 12 November, 2001.